Sleep’s Powerful Effects on the Immune System

Why consistent, restorative sleep is imperative for maintaining good health.

June 2023 | By Amy Scanlin, MS | Download Article

Despite research showing a link between adequate sleep and positive impacts on health, by some estimates 50 to 70 percent of Americans continue to suffer from sleep-related problems.¹ Whether acute (lasting one to two days) or chronic (lasting three months or more), sleep deprivation is linked to five of the top 15 leading causes of death.²

Sleep and immunity are closely linked. Sleep deprivation, even just an hour or two a night, can have negative health effects, increasing production of pro-inflammatory immune cells and changing DNA. While some inflammation is good, since it enables the body to fight infections, respond to vaccines and heal wounds, an overabundance of inflammation has the opposite effect. Increased incidence of allergies, autoimmune and neurologic disorders and even a decrease in vaccine effectiveness are just some of the possible and harmful outcomes of living in a pro-inflammatory state.

A strong immune system helps the body fight potential threats, but a body begins to attack its own healthy cells when it is on perpetual alert. And the consequences can be dire, so prioritizing quality sleep is imperative for maintaining a healthy immune system.

Biology of Healing Sleep

When given seven to eight hours of quality, uninterrupted sleep, the body repeatedly cycles through four sleep stages, with each stage lasting progressively longer. In the first two sleep stages, N1 and N2, the body slows down and prepares for its third stage, N3, which is a deep, slow-wave, restorative sleep during which recovery, improvements in the immune system and memory begin.³

It is during the fourth stage of quality, uninterrupted sleep, known as REM, that protective immunity kicks into high gear. Cytokine warning messages instruct leukocytes to find and attach to foreign invaders, and histamines promote protective swelling in response to injuries. As the night progresses, less and less time is spent in sleep stages one through three and more time is spent in stage four sleep. Healthy adults who enjoy good sleep can spend 25 percent of their sleep time in REM, but as adults age, they begin to spend progressively less time in this stage.³

Without a well-tuned internal clock that promotes adequate sleep and cycling through the sleep stages, the ability of cytokines and leukocytes to detect and kill invaders is reduced, and the protective immunity that they promote, known as adaptive immunity, is not achieved. Those with sleep apnea may have difficultly getting into deeper stages of sleep, and those with insomnia may not sleep long enough to benefit from sleep’s cumulative effects.³

Sleep appears to strengthen adaptive immunity, allowing the body to recognize and respond to pathogens. During sleep, as the body slows down, energy that would otherwise have been used during waking hours becomes available to support adaptive immune responses.

Sleep is likely the preferred time of day (or night) for these energy-heavy immune activities to occur because of the potential for deleterious effects were they to occur when we are otherwise busy with mental and physical tasks. Thus, the body has evolved to maximize adaptive immune responses during sleep.⁴

Lasting Effects of Sleep Deprivation

Insufficient REM sleep can lead to memory deficits, chronic diseases such as hypertension and type II diabetes, increased rates of glucose intolerance, hormonal changes, immune and neurodegenerative diseases, and is associated with early death. By directly altering the DNA structure inside of immune cells, sleep deprivation has a lasting effect on inflammation and inflammatory diseases.⁵

A chronic reduction in nightly sleep by three to four hours also reduces circulating natural killer cell activity to an average of 72 percent compared to a full night’s sleep, which can lead to a 1.6 time greater risk of dying of cancer.⁶

A sleep and immunity study conducted at the Icahn School of Medicine at Mount Sinai demonstrated the negative effects of sleep deprivation as study participants were progressively deprived of sleep. The study, which was broken into six-week increments, began with participants sleeping the recommended seven to eight hours; during this time, no negative immune changes were seen, as determined via blood draws. However, as the study continued and sleep was progressively reduced by 90 minutes nightly, increases in inflammatory monocyte cells were noted, as were epigenetic changes inside those cells, leading researchers to conclude that sleep restriction is likely to have negative health consequences through both an increased inflammatory state and modification of gene expression.⁷ Although the study did not directly link disease risk to sleep disorders, it did raise the question of sleep’s effects on these mechanisms.

Sleep and Allergies

Allergies are affected by circadian rhythms, and sleep deprivation may worsen their effects. For example, allergic reactions to peanuts are increased, even at a lower exposure threshold, in those who are sleep-deprived.³ Likewise, sleep deprivation directly affects asthmatic adults, causing worsening attacks, more hospitalizations and a poorer quality of life.⁸

Additionally, sleep deprivation appears to have a reciprocal effect on allergies, as found in a study of children suffering from eczema. As their sleep deprivation worsened, their symptoms worsened,⁹ leading to the question of whether sleep deprivation may indicate that allergies are not well-controlled.

Sleep and the Autoimmune System

Non-apnea sleep disorders can increase the risk of developing autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and systemic sclerosis due to a breakdown in immunologic self-tolerance, including increased production of several pro-inflammatory cytokines. Even temporary sleep deprivation may lead to a suppression of Treg cells and an excessive immune response.²

It is theorized that sleep deprivation may contribute directly to an increased susceptibility to the development of immune system diseases due to higher levels of circulating leukocytes, elevated circulating pro-inflammatory markers and reduced killer cell activity. Gene expression changes related to immune and inflammatory processes and oxidative stress were also specifically observed in those with deprived sleep.²

Numerous apparent pathologies directly link chronic sleep deprivation and immune suppression; however, more study is needed as additional factors may play a role. Fortunately, sleep disturbances are often improved in those with autoimmune disorders via autoimmune treatments.

Sleep and Neurodegenerative Diseases

It is speculated that Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, Huntington’s disease and other neurodegenerative diseases are associated with sleep deprivation, since they may be both a consequence of and a potential contributor to their cause and progression.²

A possible theory is that neuroimmune dysregulation, or the chronic activation of the immune system, may lead to neuroinflammation, proinflammatory mediators, anxiety and memory impairments in the brains of the chronically sleep-deprived.²

In both human and mice studies, acute and chronic sleep deprivation resulted in a kind of beta-amyloid (Aβ) plaque accumulation common in Alzheimer’s disease and dementia. The same has been observed in brain scans of those with self-reported sleep deprivation. Sleep deprivation may cause a reduced clearance of Aβ plaques in the cerebrospinal fluid and an increased expression of β-secretase one (BACE-1), an enzyme directly related to Aβ generation.²

It is important to note that the relationship between Alzheimer’s disease and other neurodegenerative diseases and sleep deprivation and inflammation is unconfirmed and requires further study.²

Adaptive Immunity and Vaccine Effectiveness

Adaptive immunity is particularly pertinent to vaccine effectiveness, since studies demonstrate a correlation between lack of sleep, a weakened immune response and subsequent reduction in vaccine protectiveness.⁶

Sleep deprivation appears to shift the immune system from repair mode to one of an uncontrolled inflammatory response, and it prevents vaccines from teaching the immune system to recognize antigens. In some cases, not sleeping well the night after a vaccination may necessitate the need for a second dose to achieve the desired effectiveness.

Reversing the Effects of Sleep Deprivation

Not surprisingly, controversy exists when it comes to the role of improving sleep habits and whether a reversal in the negative health effects of sleep deprivation is possible.

In the previously mentioned study conducted at Mount Sinai, a follow-on look at mice who were allowed to get 10 weeks of “good sleep,” post-sleep deprivation showed no reduction in inflammation. The immune system continued to operate at a dangerously high state, and changes to DNA rewiring were not reversed. Of course, it is worth noting that mice studies don’t always translate to human studies, and as of this publication, human studies, as well as additional mice studies looking to confirm these findings, remain incomplete.⁷

However, a study looking only at the cognitive impairments caused by sleep deprivation found some improvement is seen in participants after recovery from a 10-day sleep restriction period. Although at the end of the sleep recovery period, cognitive performance had not fully returned, indicating it can take much longer to recover from sleep debt than the length of time of sleep restriction.¹⁰

Improving Sleep Hygiene

There are many ways to improve sleep hygiene in support of more restful sleep. Less screen time, practicing relaxation and ensuring adequate and appropriate exercise — but not too close to bedtime — are among the most common sleep- promoting habits. Also, ensuring appropriate fit and use of CPAP machines in those with sleep apnea can assist with getting a better night’s sleep.

With so many ill effects of sleep deprivation across the health spectrum, getting a good night’s sleep is one of the most important things one can do to support their health.

Amy Scanlin, MS, is a freelance writer and editor specializing in medical and fitness topics.

References

1. American Sleep Apnea Association. The State of Sleep Health in America in 2022. Accessed at www.sleephealth.org/sleep-health/the-state-of-sleephealth-in-america.
2. Garbarino, S, Lanteri, P, Bragazzi, NL, et al. Role of Sleep Deprivation in Immune-Related Disease Risk and Outcomes. Nature, Nov. 18, 2021. Accessed at www.nature.com/articles/s42003-021-02825-4.
3. Suni, E. Stages of Sleep. National Sleep Foundation, Updated Jan. 26, 2023. Accessed at www.sleepfoundation.org/stages-of-sleep.
4. Suni, E. How Sleep Affects Immunity. The Sleep Foundation, April 22, 2022. Accessed at www.sleepfoundation.org/physical-health/how-sleep-affects-immunity.
5. A Consistent Lack of Sleep Negatively Impacts Immune Stem Cells Increasing Risk of Inflammatory Disorders and Heart Disease. Mount Sinai press release, Sept. 21, 2022. Accessed at www.mountsinai.org/about/newsroom/2022/a-consistent-lack-of-sleep-negatively-impacts-immune-stem-cells-increasing-risk-of-inflammatory-disorders-and-heart-disease.
6. Centers for Disease Control and Prevention. NIOSH Training for Nurses on Shift Work and Long Work Hours. Accessed at www.cdc.gov/niosh/work-hour-training-for-nurses/longhours/mod2/05.html.
7. LaMotte, S. What You Should Know About Sleep Loss and Inflammation, According to a New Study. CNN, Sept. 27, 2022. Accessed at www.cnn.com/2022/09/27/health/sleep-loss-harms-immune-system-wellness/index.html.
8. Too Little Sleep Can Mean More Asthma Attacks in Adults. American College of Allergy, Asthma and Immunology press release, May 11, 2020. Accessed at acaai.org/news/too-little-sleep-can-mean-more-asthma-attacks-in-adults.
9. Itchy Eczema and Bad Sleep in Three Million School-Aged Children. American Academy of Allergy Asthma & Immunology press release, Aug. 1, 2021. Accessed at www.aaaai.org/Tools-for-the-Public/Latest-Research-Summaries/The-Journal-of-Allergy-and-Clinical-Immunology-In/2021/itchy.
10. Newsom, R. Sleep Debt and Catching up on Sleep. The Sleep Foundation, Jan. 18, 2023. Accessed at www.sleepfoundation.org/how-sleep-works/sleep-debt-and-catch-up-sleep.